title: The clinical potential of targeted nanomedicine: delivering to cancer stem-like cells.
abstract: Cancer stem-like cells (CSCs) have been implicated in recurrence and treatment resistance in many human cancers. Thus, a CSC-targeted drug delivery strategy to eliminate CSCs is a desirable approach for developing a more effective anticancer therapy. We have developed a tumor-targeting nanodelivery platform (scL) for systemic administration of molecular medicines. Following treatment with the scL nanocomplex carrying various payloads, we have observed exquisite tumor-targeting specificity and significant antitumor response with long-term survival benefit in numerous animal models. We hypothesized that this observed efficacy might be attributed, at least in part, to elimination of CSCs. Here, we demonstrate the ability of scL to target both CSCs and differentiated nonstem cancer cells (non-CSCs) in various mouse models including subcutaneous and intracranial xenografts, syngeneic, and chemically induced tumors. We also show that systemic administration of scL carrying the wtp53 gene was able to induce tumor growth inhibition and the death of both CSCs and non-CSCs in subcutaneous colorectal cancer xenografts suggesting that this could be an effective method to reduce cancer recurrence and treatment resistance. This scL nanocomplex is being evaluated in a number of clinical trials where it has been shown to be well tolerated with indications of anticancer activity.
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors.forename: Sang-Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors.forename: Antonina
authors.initials: A
authors.lastname: Rait
authors.affiliation: SynerGene Therapeutics, Inc., Potomac, Maryland, USA.
authors.forename: Farwah
authors.initials: F
authors.lastname: Rubab
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors.forename: Abhi K
authors.initials: AK
authors.lastname: Rao
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kiritsy
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Pirollo
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors.forename: Shangzi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiner
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA. Electronic address: change@georgetown.edu.
authors.forename: Esther H
authors.initials: EH
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D016130:Immunophenotyping; D008081:Liposomes; D051379:Mice; D050997:Nanomedicine; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D011990:Receptors, Transferrin / Q000235:genetics; D019076:Transgenes; D047368:Tumor Burden / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D011990:Receptors, Transferrin; D016159:Tumor Suppressor Protein p53